title: Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection.
abstract: IgG is a major Ig subclass in mucosal secretions of the human female genital tract, where it predominates over the IgA isotype. Despite the abundance of IgG, surprisingly little is known about where and how IgG enters the lumen of the genital tract and the exact role local IgG plays in preventing sexually transmitted diseases. We demonstrate here that the neonatal Fc receptor, FcRn, is expressed in female genital tract epithelial cells of humans and mice and binds IgG in a pH-dependent manner. In vitro we show that FcRn mediates bidirectional IgG transport across polarized human endometrial HEC-1-A monolayers and primary human genital epithelial cells. Furthermore, endosomal acidification appears to be a prerequisite for FcRn-mediated IgG transcytosis; IgG transcytosis was demonstrated in vivo by translocation of systemically administered IgG into the genital lumen in WT but not FcRn-KO mice. The biological relevance of FcRn-transported IgG was demonstrated by passive immunization using herpes simplex virus-2 (HSV-2)-specific polyclonal serum, which conferred significantly higher protection against intravaginal challenge infection by the HSV-2 186 strain in WT mice than in FcRn-KO mice. These studies demonstrate that FcRn-mediated transport is a mechanism by which IgG can act locally in the female genital tract in immune surveillance and in host defense against sexually transmitted diseases.
authors.affiliation: Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.
authors.forename: Zili
authors.initials: Z
authors.lastname: Li
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Palaniyandi
authors.forename: Rongyu
authors.initials: R
authors.lastname: Zeng
authors.forename: Wenbin
authors.initials: W
authors.lastname: Tuo
authors.forename: Derry C
authors.initials: DC
authors.lastname: Roopenian
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D057900:Transcytosis / Q000187:drug effects; D014621:Vagina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014623:Vaginal Diseases / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal